The herpesviruses are the largest and most complex viruses known to be capable of inducing morphological transformation of cultured cells. They are also suspected of having a role in the initiation of several human tumors, including Burkitt's lymphoma, nasopharyngeal carcinoma and cervical carcinoma. In addition, all five human herpesviruses, herpes simplex types 1 and 2, Epstein-Barr virus, cytomegalo-virus and varicella-zoster virus are commonly harbored as long-term latent infections in most adults and can occasionally give rise to serious clinical disease especially in immunosuppressed individuals. We have been engaged in characterizing, mapping and comparing the DNA genomes of all these viruses and are paticularly interested in the biological significance of the complex arrangements of inverted repetitions, tandemly repeated segments and "translocatable-element"-like regions. Although, in general the DNA molecules differ in size and have no detectable sequence homology these repetitive "accessory" sequences in each case appear to occupy 30% of the genome and predominantly encode immediate early regulatory functions. Our studies are now focusing on detailed restriction enzyme mapping and plasmid cloning of the most interesting genes and structural features of these DNA molecules for subsequent analysis of DNA sequence homologies, regulation of gene expression and interactions with the host cell DNA.